The goals of this projects are to characterize the pathogenesis, natural history, immunology, and therapy of human herpes virus infections, with an emphasis on herpes simplex virus (HSV) and varicella-zoster (VZV) infections. Over the years we established the value, long term efficacy and safety of oral acyclovir for treatment and suppression of recurrent genital herpes and oral herpes. We defined acyclovir resistance in HSV infections in immunologically normal individuals. We studied acyclovir, and sorivudine as treatments for zoster and we have done in formal studies for treatment of postherpetic neuralgia. Major current emphases of the project involve studies of the molecular pathogenesis of HSV and VZV latency. We examine the role of HSV-1 and 2 latency-associated transcript. We have engineered specific recombinant viruses that are altered in their expression of the HSV latency transcripts and determine the impact of those mutants on virus infection, latency and reactivation. We quantitate levels of latent virus by a variey of detailed molecular techniques. We have also studied the latency and gene regulation of VZV in human tissues and defined 2 of the 4 currently known genes that are expressed in latency. Within the past year, we undertook novel studies of the seroepidemiology of human herpes tpe-8 infection, known to be associated with Kaposi's sarcoma. Also, we undertook a series of immunologic studies to define host factors that could predict symptomatic disease with HSV and frequent recurrences. These have involved HLA haplotype analyses as well as studies of cytokine release by patient cells in vitro.